High-frequency ultrasound evaluation of effects of early treatment with metoprolol on myocardial inflammatory cytokine expression in rats with acute myocardial infarction

High-frequency ultrasound evaluation of effects of early treatment with metoprolol on myocardial inflammatory cytokine expression in rats with acute myocardial infarction
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DOI:
10.1007/s11596-012-1033-3
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发表时间:
2012-10
期刊:
Journal of Huazhong University of Science and Technology [Medical Sciences]
影响因子:
--
通讯作者:
Wen Wu;Linxiao Huang;Jiang-xia Zhang;Yu Gao;Yali Yang
Wen Wu;Linxiao Huang;Jiang-xia Zhang;Yu Gao;Yali Yang
中科院分区:
其他
文献类型:
--
作者:
Wen Wu;Linxiao Huang;Jiang-xia Zhang;Yu Gao;Yali Yang

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本研究利用高频超声评估了β-肾上腺素能受体阻滞剂美托洛尔早期治疗对急性心肌梗死(AMI)后心室重塑和功能的影响。在大鼠中检查疗效与心肌炎症细胞因子表达水平之间的关系。采用结扎左前降支的方法制备AMI大鼠模型。将存活大鼠随机分为两个实验组:MI对照组(MI)和MI美托洛尔(MI-B)组,其中接受假手术的大鼠作为正常对照(Sham)。 MI-B组给予美托洛尔4周(参见CCS-2方案),另外两组通过灌胃(i.g.)给予等体积的生理盐水。治疗后4周通过高频超声评估心室重塑和功能。处死所有大鼠进行病理学检查及免疫组化检测炎症细胞因子IL-1β、IL-6、IL-10、TNF-α。与MI组相比,MI-B组左心室收缩末内径、舒张末期内径、收缩末期容积和舒张末期容积均显着减小(P<0.01),而左室前壁舒张末期厚度、射血分数和缩短分数均明显增大(P<0.01)。左心室形态和功能的显着改善与TNF-α和IL-1β表达显着减少以及IL-10表达增加相一致。我们得出的结论是,早期美托洛尔治疗AMI可以调节心肌炎症细胞因子的表达,从而改善心功能,其潜在机制可能是降低心肌细胞中促炎细胞因子的水平并增加其抗炎细胞因子的水平。我们的研究还表明,超声心动图是评估急性心肌梗死后左心室结构和功能的有用技术。
This study evaluated the effects of early treatment with β-adrenergic blocker metoprolol on ventricular remodeling and function after acute myocardial infarction (AMI) by using high frequency ultrasound. The relationship between the efficacy and the expression level of cardiac myocardial inflammatory cytokine was examined in rats. The rat model of AMI was induced by ligating the left anterior descending artery. The surviving rats were randomly assigned to two experimental groups: MI control (MI) group and MI metoprolol (MI-B) group, with the rats undergoing sham operation serving as normal control (Sham). MI-B group was given metoprolol for 4 weeks (refer to the CCS-2 protocol) and the other two groups received equal volume of saline via intragastric (i.g.) administation. The ventricular remodeling and function were evaluated by high frequency ultrasound 4 weeks after the treatment. Then all rats were sacrificed for pathological examination and immunohistochemistrical detection of inflammatory cytokines, including IL-1β, IL-6, IL-10 and TNF-α. Compared with the MI group, the left ventricular end-systolic dimension, end-diastolic dimension, end-systolic volume and end-diastolic volume of the MI-B group were significantly decreased (P<0.01), while the left ventricular anterior wall end-diastolic thickness, ejection fraction and fractional shortening were obviously increased (P<0.01). The conspicuous improvement in the left ventricular morphology and function was coincident with the markedly reduced TNF-α and IL-1β expression and the increased IL-10 expression. We are led to conclude that early metoprolol treatment for AMI can regulate myocardial inflammatory cytokine expression to improve cardiac function and the underlying mechanism might be that it decreases the level of pro-inflammatory cytokines and increases the level of its anti-inflammatory counterparts in cardiac myocytes. Our study also showed that echocardiography is a useful technique for the structural and functional assessment of left ventricle after acute myocardial infarction.